Acadia’s attempt to expand Nuplazid’s label into Alzheimer’s disease psychosis looks to have failed, following an FDA panel vote last Friday that went 9 to 3 against the idea. This was always a long shot after the complete response letter for the group’s previous application in the wider dementia-related psychosis setting; the Alzheimer’s submission relied heavily on a subgroup analysis and the FDA had already said it wanted another trial conducted. The company has yet to say whether this will happen; Alzheimer’s disease psychosis might have big commercial potential but investors are unlikely to want to see more money spent here. Either way, another CRL looks to be on the way, making negative symptoms of schizophrenia Acadia’s next label expansion bid; Nuplazid managed only a very narrow win in the first pivotal trial conducted here. Regarding the psychosis panel, the most supportive comments that Stifel analysts could muster were that the absence of negative surprises validated management’s credibility, though the logic that this is "incrementally positive" for the group’s next project, trofinetide in Rett syndrome, is pretty hard to follow. A filing for trofinetide is due mid-year, making acceptance from the FDA the next big event for Acadia.

The first test that can not only diagnose Covid but directly measure viral load has been granted emergency authorisation in the US – and its maker, Roche, needs the win. The cobas Sars-Cov-2 DuoA is a PCR test using nasal and nasopharyngeal samples that runs on the Swiss group’s cobas 6800 and 8800 systems, and should roll out in the US this month. Roche says that quantitative testing could identify infected patients earlier and more accurately than current tests. This could aid in the triage of patients, for instance by enabling swift administration of antivirals – a boon to vulnerable patients with pre-existing health conditions who need therapy fast. The launch of this test might do something to forestall the forecast drop in Roche’s test revenues. According to consensus data from Evaluate Medtech, Roche’s molecular diagnostics sales nearly doubled from 2019 to 2020 as it launched various Covid PCR tests to combat the burgeoning pandemic. However, the sellside forecasts that these sales will fall in 2022 and 2023, only returning to growth in 2024. 

With some big late-stage readouts due in Alzheimer’s disease in the coming year, Roche and AC Immune have reminded investors of the perils of this space. True, hopes were not high for the anti-amyloid MAb crenezumab, which had already flunked the pivotal Cread studies several years ago. But the latest failure, of a mid-stage trial in presymptomatic patients with a specific mutation, could make the likes of Lilly, Biogen – and indeed Roche – nervous. Roche and AC Immune are not saying much about the data, although the partners appear to disagree about whether numerical differences favouring crenezumab were “small” or not. More details are due at the AAIC meeting on August 2. The latest flop hits the theory that intervening early could halt Alzheimer’s, though the amyloid debate will rumble on, particularly as crenezumab has not been shown to reduce amyloid plaques. This has been seen with Roche’s gantenerumab, Lilly’s donanemab and Biogen/Eisai’s lecanemab. Whether plaque reduction has an impact on Alzheimer’s symptoms remains to be proven, something that pivotal data with these projects will hopefully help clarify.  

In a reminder that stents aren’t just for the vasculature, Boston Scientific has bought MI Tech, a maker of devices designed not for blood vessels but to prop open other passages such as the oesophagus and bile ducts. Boston has acquired 64% of the South Korean group from its current owner, Synergy Innovation, for KRW291.2bn ($230m). Though this is a smallish bolt-on by Boston’s historical standards, so quiet has 2022 been for M&A that, astonishingly, it qualifies as the seventh-largest acquisition of the year so far. Otherwise Boston has followed its usual MO of buying a group with which it has an existing relationship: the US company has distributed MI Tech’s Hanarostent franchise in Japan since 2015. Boston’s shares rose 4% on the news.

Nine companies have developed powered exoskeletons that are cleared for sale in the US, with almost all of these devices intended to aid walking by patients with spinal cord injury or stroke. But last week Ekso Bionics moved into an entirely new indication, as the FDA cleared its EksoNR robotic exoskeleton for use by multiple sclerosis patients. The clearance, more specifically for rehabilitation use in patients with MS, will significantly expand the device’s reach, Ekso said. It already claims that EksoNR is the latest-generation version of the “most clinically used” robotic exoskeleton on the market. Nearly a million people in the US are living with MS, according to the National MS Society, though only a small minority of these patients would be expected to develop mobility issues serious enough to warrant the use of an exoskeleton. News of the clearance prompted Ekso’s share price to close up 23% yesterday. Unfortunately the stock has lost 99% of its value since Ekso floated in early 2014, with sales having disappointed. The company is not profitable, and reported sales of just $2.6m in the first quarter of this year.

The prospects for Biomarin’s achondroplasia therapy Voxzogo in very young children had already looked murky after a vague update earlier this year. Now the company has given – some – further details, and things are still far from clear. The results, presented in a poster at the Endo meeting, came from a phase 2 study in under-fives. Biomarin touted a placebo-adjusted 0.92cm/year increase in annualised growth velocity – below the 1.57cm/year seen in a separate trial in patients aged five and over, for whom Voxzogo is already approved. What is more, the former figure included so-called “sentinel subjects” – patients who received open-label Voxzogo at the start of each new age group cohort. Biomarin did not disclose growth velocity results for randomised patients only, suggesting that these were “less good, and/or more fraught with noise”, as Stifel analysts put it. The company did give more details of Z-scores, a measure of how much a given value deviates from the mean, used to track the growth of very small children. However, the Z-score was less impressive when only randomised patients were included. Stifel reckons the latest data are “probably enough” for label expansion, but without more information this looks tough to call.

Day One Biopharmaceuticals’ stock received a much-needed boost today on data suggesting that tovorafenib might be a viable therapy for paediatric low-grade glioma. The company calls tovorafenib a type II pan-Raf inhibitor, and says most paediatric low-grade gliomas are driven by Braf alterations. The first 22 evaluable patients in the mid-stage Firefly-1 trial generated an overall response rate of 64%, comprising one unconfirmed and 13 confirmed partial responses. The trial has no control arm, but there are no approved therapies for this cancer type; Firefly-1 patients had a median of three prior lines of therapy. A larger dataset is due early in 2023, and the company hopes to file by mid-year, while a front-line pivotal study of tovorafenib, Firefly-2/Loggic, will soon get under way. Despite doubling in value today Day One is still worth 20% less than when it floated just over a year ago, though some have had skin in this game for considerably longer than IPO investors. The asset has an almost two-decade history, having been through the hands of Biogen and Takeda. Viracta, which sold off Sunesis's rights last year, might be kicking itself today.  

Crispr Therapeutics has seen impressive activity in heavily pretreated patients with T-cell lymphoma, a tough malignancy, given its CD70-directed allogeneic Car-T therapy CTX130. Unfortunately, this project has been hit with the same relapse problems as Crispr’s own and others’ off-the-shelf Cars: of the nine remissions in the company’s Cobalt-Lym trial reported at the EHA meeting on Saturday just one can be said to be long-lasting, a PR of eight months’ duration from CTX130 infusion. One short-term response is ongoing without further intervention, while one was achieved only after a second Car-T cell infusion. The remaining six responses have all relapsed, though three were retreated, and two of these went on to be transplanted. As such, Crispr’s headline ORR number of 50% across all doses, or 70% at level 3 or above, does not tell the whole story. Investors in all allo Car-T companies will be used to this story, with Caribou falling into the relapse trap just last Friday. Crispr itself has already suffered this fate with its lead off-the-shelf Car, CTX110, which hits CD19. Allogene, whose anti-CD70 Car ALLO-316 is in phase 1 for kidney cancer, will pay particularly close attention.

The unanimous backing of Bluebird's gene therapies by FDA panels last week not only throws that company a lifeline, it also gives a boost to a section of the biotech world that has taken a particularly big hit to sentiment. True, final approvals of the lentiviral projects are still pending, and reimbursement will be another issue, but comments at the hearings suggest that US physicians and patients are open to using gene therapies despite ongoing safety concerns, largely around the risk of cancer, and questions about lack of durability. For the first project, eli-cel, for a very rare childhood condition, lack of other options for those without a matched donor for stem cell transplant helped win the risk-benefit argument. A green light for beti-cel for beta thalassaemia also looks likely after the project impressed on durability, with some patients transfusion free after four years. Bluebird shares opened up 40%, but the company remains in dire financial straits. The market for eli-cel is tiny, and competition is coming behind for beti-cel. Approvals and the swift sale of subsequent priority review vouchers must happen without delay for these gene therapy stories to have a chance of a happy ending.

The soon-to-be pure-play pharma company GSK desperately needed a hit in respiratory syncytial virus – the vaccine for older adults is considered its most valuable pipeline project. Relief all round then at news of success for the phase 3 Aresvi 006 trial, though lack of detail makes the extent of the win unknowable. GSK described the result as “statistically significant and clinically meaningful”, adding that the effect size was consistent across secondary endpoints and in those aged 70 and above. The company has previously described efficacy above 50% as clinically meaningful, 70% very good and above 80% outstanding; analysts want to see at least 70%, believing that anything less would leave GSK susceptible to projects coming behind. Durability of response is another consideration, with some analysts concerned that regulators might want to see data over more than one RSV season. GSK is confident that its vaccine, which uses the same adjuvant as Shingrix, will provide long-term protection; this is an issue that all contenders must address, of course, and could be an important differentiator in the long term. With Pfizer and J&J also expecting pivotal readouts later this year, the race to market will soon be on.